AUTHOR=Rescigno Maria , Agrati Chiara , Salvarani Carlo , Giannarelli Diana , Costantini Massimo , Mantovani Alberto , Massafra Raffaella , Zinzani Pier Luigi , Morrone Aldo , Notari Stefania , Matusali Giulia , Pinter Giuseppe Lauria , Uccelli Antonio , Ciliberto Gennaro , Baldanti Fausto , Locatelli Franco , Silvestris Nicola , Sinno Valentina , Turola Elena , Lupo-Stanghellini Maria Teresa , Apolone Giovanni , the VAX4FRAIL study Group , Apolone Giovanni , Mantovani Alberto , Costantini Massimo , Silvestris Nicola , Agrati Chiara , Ciceri Fabio , Locatelli Franco , Mantovani Alberto , Morrone Aldo , Tommasino Massimo , Silvestris Nicola , Pinter Giuseppe Lauri , Uccelli Antonio , Zinzani Pier Luigi , Corradini Paolo , Ciliberto Gennaro , Salvarani Carlo , Uccelli Antonio , Rescigno Maria , Fenoglio Daniela , Mortarini Roberta , Conti Laura , Mandoj Chiara , Lizier Michela , Croci Stefania , Garrisi Vito , Baggi Fulvio , Lazzarotto Tiziana , Bonifazi Francesca , Quintarelli Concetta , Carsetti Rita , Girardi Enrico , Bettini Aurora , Bordoni Veronica , Castilletti Concetta , Cimini Eleonora , Casetti Rita , Colavita Francesca , Cristofanelli Flavia , Francalancia Massimo , Gili Simona , Goletti Delia , Gramigna Giulia , Grassi Germana , Lapa Daniele , Leone Sara , Mariotti Davide , Matusali Giulia , Meschi Silvia , Notari Stefania , Puro Enzo , Rubino Marika , Sacchi Alessandra , Tartaglia Eleonora , Corradini Paolo , Damian Silvia , Marasco Vincenzo , de Braud Filippo , Stanghellini Maria Teresa Lupo , Dagna Lorenzo , Ogliari Francesca , Filippi Massimo , Bruno Alessandro , Catalano Gloria , Nitti Rosamaria , Mengarelli Andrea , Marchesi Francesco , Minuti Giancarlo Paoletti e Gabriele , Papa Elena , Azzolini Elena , Germagnoli Luca , Selmi Carlo , De Santis Maria , Carlo-Stella Carmelo , Bertuzzi Alexia , Motta Francesca , Ceribelli Angela , Miggiano Chiara , Fornasa Giulia , Baldanti Fausto , Monti Sara , Montecucco Carlo Maurizio , Morrone Aldo , Graceffa Dario , Catanoso Maria Grazia , Guberti Monica , Pinto Carmine , Merli Francesco , Valzania Franco , Divella Rosa , Tufaro Antonio , Garrisi Vito , Delcuratolo Sabina , Miano Mariana , Antozzi Carlo , Frangiamore Silvia Bonanno Rita , Maggi Lorenzo , Uccelli Antonio , Pronzato Paolo , Inglese Matilde , Genova Carlo , Lapucci Caterina , Laroni Alice , Poiré Ilaria , Fusconi Marco , Stefoni Vittorio , Pantaleo Maria Abbondanza , Giannarelli Diana , Sinno Valentina , Di Cosimo Serena , Turola Elena , Pulice Iolanda , Fondazione Roberta Mennitto , Trinca Stefania , Piaggio Giulia , Pozzi Chiara , Cassaniti Irene , Barberini Alessandro , Delcuratolo Sabina , Elena Rinaldi , Bortone Federica , Dal Bello Maria Giovanna , Corazza Silvia TITLE=Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1104124 DOI=10.3389/fimmu.2023.1104124 ISSN=1664-3224 ABSTRACT=Introduction

Immunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.

Methods

Here we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.

Results

We show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.

Discussion

These data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20.